The present invention relates to (2,4,6-trimethoxyphenyl)-(3-piperidinopropyl)-ketone derivatives as novel industrial products. The invention also relates to the uses in therapeutics and the process of synthesis of these novel derivatives.
It is known that in the past a certain number of compounds of the phenyl-aminoalkyl-ketone type have been suggested where the amino residue is particularly a piperidino group. In particular there are known:
from French Patent No. 1 492 256, from the French Patent (BSM) No. 5636M and from the article of A. BOUCHERLE et al., Chimie Therapeutique, 3 (No. 4), 256-259 (1968), the (2,4,6-trimethoxyphenyl)-[2-piperidino-ethyl]-ketone, (2,4,6-trimethoxyphenyl)- [2-(4-methylpiperidino)-ethyl]-ketone and [(2,4-dimethoxyphenyl)-[2-(2-methylpiperidino)-ethyl]]-ketone which have essentially anti-inflammatory, antalgic and antipyretic effects, on the one hand, and (2,4,6-trimethoxyphenyl)-[(2-methylpiperidino)-methyl]-ketone, which is a neuroleptic agent, on the other hand;
from British Patent No. 1,115,992, (2,4-dimethoxyphenyl)-(piperidinomethyl)-ketone and (2,4,6-trimethoxyphenyl)- [(4-methylpiperidino)-methyl]-ketone, which have essentially anti-spasmodic and tranquillising effects; and,
from U.S. Pat. No. 3,895,030, (2,4,6-trimethoxyphenyl)-(3-piperidinopropyl)-ketone hydrochloride, which has essentially anti-spasmodic effects and which is useful in the treatment of renal colic, and (2,4,6-trimethoxyphenyl)-(3-pyrrolidinopropyl)-ketone hydrochloride (Code No. LL 1656), which is a reference peripheral vasodilator, which has formed the subject of publication by DEBRAY et al., Therapie, 30, 259-266 (1975) and which is marketed in pharmacy under the name of "FONZYLANE" (International Common Name: BUFLOMEDIL HYDROCHLORIDE).
Lastly, it is known particularly from British Patent No. 2,004,883 and from European patent application No. 82,400,577.1, that there is no structure-activity relationship within the family of (alkoxy and hydroxyphenyl)-aminoalkyl-ketones, the pharmacological effects being modified or disappearing according to the nature of the substituents of the phenyl group, the nature of the amino group, and lastly, the nature of the alkyl group present between the CO group and the amino group.
It is known in particular from the aforesaid European patent application that (2,6-dimethoxy-4-hydroxyphenyl)-(3-piperidinopropyl)-ketone hydrochloride (Code No.: CRL 40,746) is a vasodilator agent whereas its isomer (2,4-dimethoxy-6-hydroxyphenyl)-(3-piperidinopropyl)ketone hydrochloride (Code No.: CRL 40,747) is devoid of pharmacological interest as a vasodilator substance by the intravenous route.